Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (ESsCOVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04576728
Recruitment Status : Recruiting
First Posted : October 6, 2020
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Biotest

Brief Summary:

The objectives of the trial are to evaluate the efficacy and safety of trimodulin as add-on therapy to standard of care (SoC) compared to placebo treatment in adult hospitalized subjects with severe COVID-19.

Additionally, pharmacodynamic (PD) and pharmacokinetic (PK) properties of trimodulin will be evaluated in all subjects.


Condition or disease Intervention/treatment Phase
Covid19 Drug: Trimodulin Other: Placebo (human albumin 1%) Phase 2

Detailed Description:

This is a randomized, placebo-controlled, double-blind, multi-center, phase II trial investigating the efficacy and safety of trimodulin compared to placebo treatment, as add-on therapy to SoC in adult subjects with severe COVID-19. Severe COVID-19 patients with need for non-invasive ventilation or high flow oxygen and with dysregulated inflammatory responses demonstrated by an elevated CRP level, will be enrolled.

Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by center. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five consecutive days (day 1 through day 5) as add-on therapy to SoC. The subsequent follow-up phase comprises 23 [+3] days (day 6 through day 28) followed by an end-of-trial visit/ telephone call on day 29 [+3]. For evaluation of this trial, a 9-category ordinal scale will be used. The primary aim of trimodulin treatment in the enrolled severely ill patients with a score of 5, is to prevent their clinical deterioration to a critical disease stage (score 6-7, e.g. requiring invasive mechanical ventilation or ECMO) and death (score 8). Accordingly, a composite primary efficacy endpoint reflecting the deterioration / mortality rate is used.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized on a 1:1 basis either to trimodulin or to placebo treatment stratified by center.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: All bottles will be indistinguishable.
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase II Trial Investigating the Efficacy and Safety of Trimodulin (BT588) as add-on Therapy to Standard of Care in Adult Subjects With Severe COVID-19
Actual Study Start Date : October 6, 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Trimodulin
Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
Drug: Trimodulin
IMP will be administered via IV infusion on 5 consecutive days.
Other Name: BT588

Placebo Comparator: Placebo
Human albumin 1%
Other: Placebo (human albumin 1%)
IMP will be administered via IV infusion on 5 consecutive days.




Primary Outcome Measures :
  1. Clinical detoriation rate [ Time Frame: Between day 6 and day 29 ]
    Percentage of subjects with a change of clinical status to score 6 or 7 on the 9-category ordinal scale

  2. 28-day all-cause mortality rate [ Time Frame: Between day 1 and day 29 ]
    Percentage of subjects with a change to score 8 on the 9-category ordinal scale


Secondary Outcome Measures :
  1. Clinical deterioration rate [ Time Frame: Days 1-29 and days 6-29 ]
    Percentage of subjects with a change to score 6-7

  2. 28-days all-cause mortality rate on day 29 [ Time Frame: Day 29 ]
    Percentage of subjects with score=8, assessed at the end-of-trial visit on day 29 [+3].

  3. Time to clinical deterioration [ Time Frame: Time Frame: between Days 1-29 and days 6-29 ]
    Number of days to first change from score 5 (enrollment) to score 6-7

  4. Time to Mortality [ Time Frame: Time Frame: between Day 1 and day 29 ]
    Number of days to change to score =8

  5. Proportion of subjects in each of the 9-categories of the ordinal scale [ Time Frame: Days 7, 14, 21, 29 ]
    Number of patients by score on specific study days

  6. Time to clinical improvement [ Time Frame: Day 29 ]
    Number of days to change to score 4 (mild disease, with supplemental oxygen) or score 3 (mild disease, no supplemental oxygen)

  7. Proportion of subjects with score ≤2 [ Time Frame: Day 29 ]
    Proporation of subjects that improved to score ≤2

  8. Days on IMV [ Time Frame: Until day 29 ]
    Number of calendar days on IMV until day 29

  9. Days without oxygen supply [ Time Frame: Until day 29 ]
    Number of calendar days without any form of oxygen support until day 29

  10. Time to discontinuation from any form of oxygen supply [ Time Frame: Until day 29 ]
    Time to definite stop of any form of additional oxygenation, irrespective of short interruptions

  11. Proportion of subjects without any form of oxygen supply [ Time Frame: Day 29 ]
    Proportion of subjects that improved to not requiring supplemental oxygen.

  12. Hospital-free-days [ Time Frame: Until day 29 ]
    Calendar days between hospital discharge and day 29

  13. SARS-CoV-2 status [ Time Frame: Until day 29 ]
    Time to SARS-CoV-2 negative status

  14. Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest, infusional TEAEs [ Time Frame: Until day 29 ]
    Number, severity, causality, outcome, and seriousness of all. AE, TEAEs that led to permanent withdrawal of IMP, and TEAEs that led to discontinuation of the trial.

  15. TEAEs [ Time Frame: Until day 29 ]
    Number of all infusion related TEAEs

  16. SAEs [ Time Frame: Until day 29 ]
    Number, severity, causality, and outcome of all SAEs

  17. Dose modifications [ Time Frame: Day 1-5 ]
    Dose modifications (incl. reductions and changes in infusion rate)

  18. Time to recovery [ Time Frame: Day 29 ]
    Number of days to change to score ≤2 (hospital discharged or meets discharge criteria)

  19. Change over time in ECG parameters [ Time Frame: Until day 29 ]
    ECG recordings, (including heart rate, PR interval, RR interval, QRS interval, QT-interval, QTcF) showing abnormal, clinically relevant findings will be reported as adverse event.

  20. Change over time in vital signs [ Time Frame: Until day 29 ]
    Changes in recordings of vital sign parameters (including systolic and diastolic blood pressure, Arterial oxygen saturation, heart rate, respiratory rate and body temperature) showing clinically significant measurements outside the normal range will be reported as adverse event.


Other Outcome Measures:
  1. Pharmacokinetic assessment of immunoglobulins [ Time Frame: Day 1(baseline) to day 29 ]
    Assessment of changes in serum concentrations (g/L) of IgM, IgA, and IgG before, during and after treatment.

  2. Pharmacodynamic assessment of disease related serum proteins [ Time Frame: Day 1(baseline) to day 29 ]
    Assessment of relative changes in serum concentrations from baseline before, during and after treatment including inflammation markers (e.g. % change in CRP, PCT, Ferritin, TNF-alpha, IL-6, IL-8 and IL-10), biomarkers (e.g. % change in p-selectin) and complement factors (e.g. % change in C3, C4).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained from the subject or legally authorized representative or informed verbal or administration consent due to pandemic situation, in compliance with all local legal requirements.
  2. Male or female subject ≥18 years of age.
  3. Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract sample within the last 5 days at screening.
  4. Diagnosis of community-acquired severe COVID-19 within 10 days after hospital-admission, with severe defined as:

    Need for non-invasive ventilation (NIV), or high-flow oxygen therapy (score =5 on the 9-category ordinal scale).

    At least one of the following clinical respiratory parameters is fulfilled: dyspnea, respiratory frequency ≥30/min, SpO2 ≤93%, 100 mmHg < PaO2/FiO2 ≤300 mmHg, and/or lung infiltrates >50% within 24 to 48 hours.

    At least one measurement of C-reactive protein ≥50 mg/L within 36 hours prior to start of treatment.

  5. Subject must receive SoC treatment for COVID-19.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Subjects that deteriorated to score >5 on the 9-category ordinal scale (e.g. receiving invasive mechanical ventilation (IMV), and/or extracorporeal membrane oxygenation (ECMO)) or subjects that improved to score <5 prior to randomization.
  3. Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start of treatment.
  4. Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start of treatment.
  5. Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment.
  6. Known hemolysis.
  7. Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs (e.g. cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis) within the previous 3 months or those subjects particularly at risk for TEEs (e.g. history of thrombophilia, permanent immobilization, or permanent paralysis of the lower extremities) caused by other reasons than COVID-19.
  8. Subject on dialysis or with severe renal impairment, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² assessed within 24 hours prior to start of treatment (details in Appendix 3: Estimated Glomerular Filtration Rate).
  9. Subject with end stage renal disease (ESRD), or known primary focal segmental glomerulosclerosis (FSGS).
  10. Known severe lung diseases interfering with COVID-19 therapy (e.g. severe interstitial lung disease, cystic fibrosis, idiopathic pulmonary fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
  11. Known decompensated heart failure (New York Heart Association class III-IV).
  12. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score ≥9 points), or hepatocellular carcinoma.
  13. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin.
  14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.
  15. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months.
  16. Known human immunodeficiency virus infection.
  17. Life expectancy of less than 90 days, according to the Investigator's clinical judgment, because of medical conditions neither related to COVID-19 nor to associated medical complications.
  18. Obesity (body mass index ≥40 kg/m²), a body weight of more than 123 kg, or anorexia (body mass index <16 kg/m²).
  19. Known immunosuppressive treatment other than acute treatment for COVID-19 (e.g. transplant recipient, subject with autoimmune disease).
  20. Known treatment with polyvalent immunoglobulin preparations, any type of blood product, or any type of interferon during the last 21 days before entering the trial.
  21. Participation in another interventional clinical trial within 30 days before entering, or during the trial, or previous participation in this clinical trial.
  22. Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04576728


Contacts
Layout table for location contacts
Contact: Patrick Langohr +491732947122 patrick.langohr@biotest.com
Contact: Iris Bobenhausen, Dr. +49 1522 280 1073 iris.bobenhausen@biotest.com

Locations
Layout table for location information
Brazil
Investigational site # 5503 Recruiting
Porto Alegre, Brazil, 90020-090
Investigational site # 5502 Recruiting
Santo André, Brazil, 09030-010
Investigational site # 5505 Recruiting
Santo André, Brazil, 09080-110
Investigational site # 5501 Recruiting
São Paulo, Brazil, 05403-000
France
Investigational Site # 3301 Recruiting
Paris, France, 75877
Investigational site # 3305 Recruiting
Saint-Étienne, France, 42 055
Russian Federation
Investigational site # 0702 Recruiting
Moscow, Russian Federation, 111539
Investigational Site # 0704 Recruiting
Moscow, Russian Federation, 125367
Investigational site # 0701 Recruiting
Saint Petersburg, Russian Federation, 197706
Spain
Investigational Site # 3401 Recruiting
Barcelona, Spain
Investigational Site # 3402 Recruiting
Madrid, Spain
Sponsors and Collaborators
Biotest
Investigators
Layout table for investigator information
Principal Investigator: Antoni Torres, MD University of Barcelona Hospital Clinic of Barcelona Spain
Layout table for additonal information
Responsible Party: Biotest
ClinicalTrials.gov Identifier: NCT04576728    
Other Study ID Numbers: 998
First Posted: October 6, 2020    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biotest:
Covid19
Severe community acquired pneumonia
Acute Respiratory Distress Syndrome
SARS-CoV-2
Severe Corona Virus Disease